Calcium Channel Blockers (CCBs) PDF

█ Calc cium chan nnel bloc ckers (CC CBs) These a are drugs that t block voltage-g gated 2+ Ca ch hannels. Classiffication off CCBs ac ccordin...

█ Calc cium chan nnel bloc ckers (CC CBs) These a are drugs that t block voltage-g gated 2+ Ca ch hannels. Classiffication off CCBs ac ccording to o tissue selectivityy CCBB with mainly cardiaac effects: vera apamil, diiltiazem. CCB B with mainly vascular effectss (dih hydropyridiines): nifed dipine, amlodipine, nimodipin n pine e, nicardip CCBB with main effect on n other tis ssue: flun narizine, cinnarizine c e Pharm macologica al effects CVS Nifedip pine Diltiazem D Vera apamil Heart: - Neggative inotrropic effec ct — ++ +++ - A-VV conductioon — ↓↓ ↓↓↓ - HR ↑ (refle ex) ↓ ↓↓ ↓ Blood vessels: - Corronary VD +++ + ++ ++ + - Peripheral VDD +++ + ++ ++ + - Bloood pressurre ↓↓↓ ↓ ↓ ↓ Other e effects  Theey relax all smooth muscles (v (vascular, bronchial, b GIT, uterin ne, etc.).  Theey ↓ Ca - mediated 2+ m cell c necro osis and ap poptosis.  Verrapamil ↓ in ase from pa nsulin relea ancreatic beta b cells bu ut of little cllinical significance. Therap peutic use es ▌Cardiio-selectiv ve CCBs (v verapamill & diltiaze em): Isch hemic hea art disease e (IHD): – They ↓↓ myocardial contractilit c ty and myoocardial O2 demand. – They prod duce coronnary VD and d ↑ corona ary blood flow. – They ↓ Ca - mediate 2 2+ ed myocytte cell necrrosis. 157  B. vasculosselective CCBs N.B C (dihyydropyridinnes) e.g niifedipine aare also be eneficial in IIHD but they cause e conside erable peripheral VD D, so the dose sho ould be adju usted to avvoid hypotension andd reflex tac chycardia. Carrdiac arrhy ythmias: supravent s ricular tac chycardia (SVT): – SVT includ de atrial flu utter, fibrilla ation, paro oxysmal atrial tachyccardia, etc. – Verapamil ↓ AV cond duction, so o it protec cts the ven ntricles fro om the rappid atrial rate (also β-blockers β s have the same effect). B. Nifedipine is contraindicated a N.B as it causes s hypotens sion and refflex tachyc cardia. Hyp pertrophic c obstructive cardio omyopathy y (HOCM):: – In hypertrophic obsstructive caardiomyop pathy, the wall of the left ventricle v and interve entricular septum is s much thickened leading to o narrowin ng of the aortic outtlet and on of blood obstructio d flow. – Increasing g contracttility worse ens the obstruction o n while decreasingg contracttility reduc es resistan nce to blood flow through the aortic ou utlet and im mprove exerrcise tolera ance. B. Nifedipin N.B ne is contra aindicatedd because it produce es reflex hycardia → worsening tach g of the ou utflow obsttruction. Arte erial hypertension: – They ↓ myyocardial contractilityy and COP. – They causse periphe eral VD d ue to ↓ CaC 2+ influx x in the vascular smooth s ms s. ▌Vascu ulo-selecttive CCBs (Nifedipin ne and am mlodipine)::  Arteerial hyperttension.  Perripheral vascular v disease (e.g. Ray ynaud’s disease d aand intermittent udication): to improve peripherral microcirrculation. clau  Nife edipine is sometimes used to rrelax the uterus u and delay pretterm labor..  Nim modipine has h high afffinity for c cerebral BV V. It is use ed for preveention of cerebral c vasospasm an nd ischemia complic cating sub barachnoid hemorrhaage. Advers se effects Verrapamil & diltiazem:: – Bradycard dia and hea art block. – Worsening g of CHF (d due to theiir –ve inotrropic effectt). – Constipatiion due to ↓ GIT mottility. 158  Nife edipine: – Hypotension and refflex tachyccardia. – Gingival (g gum) hyperrplasia. – Salt & watter retentio on (=ankle edema; more com mmon than with verappamil due to significa ant VD and d hypotenssion). Contra aindication ns & preca autions Verapa amil & diltiazem: – Con ngestive he eart failure e. – Braadycardia and a heart block. b – Wolff-Pakinso on-White syndrome: s  In WPW syndrom me, there e is accessoryy conducting path hway between atria a and ventricles v o other tthan the e normal AV sysstem causing a uniqu ue type of atrioventric cular re-en ntry tachyc cardia.  A As a rule, most druggs that ↓ A AV nodal co onduction (Adenosinne; Beta-bllockers; CCBs; Dig goxin) can paradoxic cally ↑ the conduction in the ab bnormal pathway p leading to worseningg of the tac chycardia.  W WPW syndrome can be man naged by amiodaro a ne but deefinitive tre eatment aser ablatio includes la on of the a accessory pathway (s see later). – Veraapamil sh hould not be comb h digitalis or β-blo bined with ockers as it may agg gravate bra adycardia caused c byy these dru ugs (nifedip pine is the drug of ch hoice to be u used with β-blockers β s because it doesn't cause braddycardia). Nifedip pine: – Hyp potension. – Hyp pertrophic obstructiv ve cardiom yopathy (H HOCM) Wh hy? – Unsstable angina (risk off reflex tachhycardia). – Sup praventricuular tachyccardia (SVT T) Why? 159